Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

The conversion of tetrazolo[1,5-a]quinoxalines to 1,2,3-triazoloquinoxalines and triazoloimidazoquinoxalines under typical conditions of a CuAAC reaction has been investigated. Derivatives of the novel compound class of triazoloimidazoquinoxalines (TIQ) and rhenium(I) triazoloquinoxaline complexes as well as a new TIQ rhenium complex were synthesized. As a result, a small 1,2,3-triazoloquinoxaline library was obtained and the method could be expanded towards 4-substituted tetrazoloquinoxalines. The compatibility of various aliphatic and aromatic alkynes towards the reaction was investigated and the denitrogenative annulation towards imidazoloquinoxalines could be observed as a competing reaction depending on the alkyne concentration and the substitutions at the quinoxaline.


Synthesis of starting materials:
Scheme S1: Synthesis of starting materials for the CuAAC reaction.
In addition, phenylacetylene 4a as an aromatic alkyne was tested under analogous conditions. Denitrogenative annulation to compound S9 could be observed as expected and in similar yields to the reaction with hexyne (see entry 9, Table S2).
Indications for a pressure-dependancy of the reaction were found when using different reaction vessels such as vials and flasks (see entries 1, 2 and 3 in Table S3); however, no conclusive result could be obtained when applying this method to other derivatives. To ensure proper reproducability, reaction vessels are given below.
S8 Table S3: Full results for screening of different reaction conditions regarding the denitrogenative annulation with tetrazolo [1,5-a]quinoxaline 11d. Standard conditions: argon atmosphere, 0.1 equiv. of (CuOTf) 2 •C 6 H 6 , 2 equiv hexyne, toluene, 100 °C, 3 d.  Mechanistical studies: The denitrogenative annulation was conducted with 11d and addition of TEMPO in comparison to the reaction without any additives. No changes in the yield of the imidazole product 16c were observed, indicating that the reaction does not occur via a radical pathway as described by Roy et al. [7].

NMR of triazole vs imidazole products:
Triazole and imidazole products show noticeable differences in the 1 H NMR chemical shift of the triazole and imidazole hydrogen atoms ( Figure S1). Whereas the imidazole signals are usually located around 7.5 ppm, the triazole signals can be found at 8 ppm and higher with the exception of 15c (signal at 7.66 ppm). The shifts are in accordance with the shifts reported in literature for similar products. [6,7] Figure S1: Excerpt from the aromatic region of the 1 H NMR spectra of two respective imidazole (16b, 16h) and triazole products (15b, 15h). The signals of the triazole H (green frame) are shifted into the deep-field significantly compared to their imidazole counterparts (blue frame).
The same behavior could be observed for the signals of the obtained triazoloimidazoquinoxalines (see Figure S2). In the 1 H NMR spectrum, both triazole and imidazole signals could be differentiated-whereas the triazole signal was located at 9.07 ppm, the imidazole singulet signal could be observed at 7.66 ppm for derivate 25a.
S10 Figure S2: Excerpt from the aromatic region of the 1 H NMR spectra of TIQ 25a. The signals of the triazole H (green frame) are shifted into the deep-field significantly compared to their imidazole counterparts (blue frame).

2-Chloroquinoxaline
The synthesis of this compound has been previously described and the NMR data corresponds with the literature [13].

S23
The synthesis of this compound has been previously described and the NMR data corresponds with the literature [13].

S27
The starting material 2-chloro-3-phenylquinoxaline (899 mg, 3.74 mmol, 1.00 equiv) was dissolved in 10 mL of DMF and sodium;azide (271 mg, 4.17 mmol, 1.12 equiv) was added; the reaction mixture was stirred at 80 °C for 2 h. The reaction mixture was cooled to 25 °C and distilled water was added, then the organic phase was separated and the aqueous phase was extracted 3× with EtOAc. The combined organic phases were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude product was purified via column chromatography (dryload on Celite, cHex -> eluent cHex/ethyl acetate 1:1) and 4-phenyltetrazolo [1,5-a]quinoxaline (865 mg, 3.50 mmol, 94% yield) was obtained as a colorless solid. The use of this compound has been previously described in literature [19].

S35
The product was obtained as a yellow solid in 88% yield (432 mg, 2.22 mmol) that turns orange after contact with air for some days. The synthesis of this compound has been previously in literature [7]. The starting material tetrazolo [1,5-a]quinoxaline (50.0 mg, 292 μmol, 1.00 equiv) and palladium (10% on active charcoal, 31.1 mg, 29.2 μmol, 0.100 equiv) were added to a flame-dried flask and the flask was evacuated. Then 2.5 mL of DMF was added and the reaction mixture was stirred under a hydrogen gas atmosphere for 19 h. Water and EtOAc were added and the aqueous phase was extracted 3× with ethyl acetate. The combined organic layers were dried over Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified via column chromatography (dryload on Celite, cHex -> ethyl acetate) and 4,5-dihydrotetrazolo [1,5-a]quinoxaline (44.0 mg, 254 μmol, 87% yield) was obtained as a colourless solid. The synthesis of this compound has been previously in literature [23].